Avtor/Urednik		Bonnefoi, Herve; Piccart, Martine; Bogaerts, Jan; Čufer, Tanja
Naslov		TP53 status for prediction of sensitivity to taxane versus non-taxane neoadjuvant chemotherapy in breast cancer (EORTC 10994/BIG 1-00): a randomised phase 3 trial
Tip		članek
Vir		Lancet Oncol
Vol. in št.		Letnik 12, št. 6
Leto izdaje		2011
Obseg		str. 527-39
Jezik		eng
Abstrakt		Background: TP53 has a crucial role in the DNA damage response. We therefore tested the hypothesis that taxanes confer a greater advantage than do anthracyclines on breast cancers with mutated TP53 than in those with wild-type TP53. Methods: In an open-label, phase 3 study, women (age <71 years) with locally advanced, inflammatory, or large operable breast cancers were randomly assigned in a 1:1 ratio to either a standard anthracycline regimen (six cycles of intravenous fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2 every 21 days [FEC100], or fluorouracil 600 mg/m2, epirubicin 75 mg/m2, cyclophosphamide 900 mg/m2 [tailored FEC] starting on day 1 and then every 21 days) or a taxane-based regimen (three cycles of docetaxel 100 mg/m2, intravenously infused over 1 h on day 1 every 21 days, followed by three cycles of intravenous epirubicin 90 mg/m2 and docetaxel 75 mg/m2 on day 1 every 21 days [T-ET]) at 42 centres in Europe. Randomisation was by use of a minimisation method that stratified patients by institution and initial tumour stage. The primary endpoint was progression-free survival (PFS) according to TP53 status. Analysis was by intention to treat. This is the final analysis of this trial. The study is registered with ClinicalTrials.gov, number NCT00017095. Findings: 928 patients were enrolled in the FEC group and 928 in the T-ET group. TP53 status was not assessable for 183 (20%) patients in the FEC group and 204 (22%) patients in the T-ET group mainly because of low tumour-cell content in the biopsy. 361 primary endpoint events were recorded in the FEC group and 314 in the T-ET group. In patients with TP53-mutated tumours, 5-year PFS was 59-5% (95% CI 53-4-65-1) in the T-ET group (n=326) and 55-3% (49-2-60-9) in the FEC group (n=318; hazard ratio 0-84, 98% CI 0-63-1-14; p=0-17). (Abstract truncated at 2000 characters)
Deskriptorji		BREAST NEOPLASMS CHEMOTHERAPY, ADJUVANT NEOPLASM STAGING FLUOROURACIL EPIRUBICIN CLINICAL TRIALS, PHASE III CYCLOPHOSPHAMIDE PROTEIN P53 SURVIVAL ANALYSIS